News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2020)

To better understand the extent of their associated adverse events, Bleecker et al (Am J Respir Crit Care Med 2019 Sep 16; https://doi.org/10.1164/rccm.201904-0903SO ) performed a systematic literature review examining the real-world use of systemic corticosteroids in patients with asthma. Systemic corticosteroids were more frequently used in patients with severe disease, with short-term use being more common than long-term use. However, both short-term and long-term treatment increased the risk of acute and chronic adverse events, even with relatively low doses. Finally, the authors identified more prevalent use of systemic corticosteroids than suggested by guidelines. These findings emphasize that systemic corticosteroids are overused for the treatment of asthma.More prevalent use of systemic corticosteroids than suggested by guidelines More prevalent use of systemic corticosteroids than suggested by guidelines We asked first author Eugene Bleecker, MD, of the University of Arizona Health Sciences in Tucson, Arizona, to comment on the article. He writes, “In managing patients with severe asthma, we need to be more aware of the short and long term adverse side effects of systemic corticosteroids. We should minimize exposure and seek alternative therapies.” Three recently published phase 2 trials have shown the efficacy of mAb biologics in allergic patients. Hirano et al (Gastroenterology 2019; https://doi.org/10.1053/j.gastro.2019.09.042 ) found that dupilumab, which specifically targets the IL-4 receptor to inhibit the signaling of both IL-4 and IL-13, reduced clinical symptoms and histologic and endoscopic disease severity in patients with eosinophilic esophagitis. Maurer et al (N Engl J Med 2019;381:1321-32; https://doi.org/10.1056/NEJMoa1900408 ) demonstrated that the high-affinity IgE-neutralizing mAb ligelizumab increased the rate of disease relapse in patients with chronic spontaneous urticaria, even compared with omalizumab. Finally, Chen et al (Sci Transl Med 2019;11; https://doi.org/10.1126/scitranslmed.aax2945 ) identified that etokimab, which neutralizes IL-33, decreased symptom severity in adults with atopic dermatitis. Collectively, these trials highlight the exciting potentials of biologics and rapid developments in the allergy field. Figure from Wikimedia Commons - Public Domain (user Genatur).Exciting potentials of biologics and rapid developments in the allergy field Exciting potentials of biologics and rapid developments in the allergy field Virchow et al (Lancet 2019; https://doi.org/10.1016/S0140-6736(19)32215-9 ) recently performed 2 concurrent trials (TRIMARAN and TRIGGER) examining the efficacy of a single inhaler containing a long-acting muscarinic antagonist, an inhaled corticosteroid (ICS), and a long-acting β-agonist (LABA) in adults with uncontrolled asthma. The TRIMARAN study included participants receiving a medium dose of ICS plus a LABA, whereas the TRIGGER trial focused on patients receiving high doses of an ICS plus a LABA. In both trials the single-inhaler triple therapy improved lung function and decreased the rate of exacerbations compared with values in patients receiving ICS + LABA treatment alone. The findings from these 2 trials raise the exciting possibility of treating severe uncontrolled asthma with one combination triple-therapy inhaler.Single-inhaler triple therapy improved lung function and decreased the rate of exacerbations Single-inhaler triple therapy improved lung function and decreased the rate of exacerbations We asked first author J. Christian Virchow, MD, of Universitätsmedizin Rostock in Rostock, Germany, to comment on the article. He writes, “Triple inhalation therapy for asthma in the past has always required at least 2 different inhalers adding to the complexity and the possibility of errors with inhalation therapy. The present studies show that inhalation of a triple therapy with ultra-fine particles not only improves pulmonary function but also reduces exacerbations.” The neuropeptide calcitonin gene-related peptide (CGRP) has been shown to negatively regulate group 2 innate lymphoid cell (ILC2) responses in patients with intestinal allergic inflammation (Immunity 2019;51:696-708, e9; https://doi.org/10.1016/j.immuni.2019.09.004 ) and in the lungs during allergic airway inflammation (Wallrapp et al; Immunity 2019;51:709-23, e6; https://doi.org/10.1016/j.immuni.2019.09.005 ) or in response to helminth infection (Nagashima et al; Immunity 2019;51:682-95, e6; https://doi.org/10.1016/j.immuni.2019.06.009 ). In addition to neurons, ILC2s expressed both CGRP and its cognate surface receptor. CGRP inhibited activation of ILC2s in response to alarmins, such as IL-33, and during helminth infection to constrain type 2 immunopathology. These results demonstrate a novel neuronal-ILC2 cross-talk during type 2 inflammation, which represents a very promising therapeutic target for the treatment of allergic diseases. Figure from Wikimedia Commons – Public Domain (User Dana Scarinci Zabaleta).Neuronal-ILC2 cross-talk during type 2 inflammationNews items were written by medical writer Jared Travers, MD, PhD. Neuronal-ILC2 cross-talk during type 2 inflammation News items were written by medical writer Jared Travers, MD, PhD.